Evaluation of COVID-19 Vaccines in Primary Prevention Against Infections and Reduction in Severity of Illness Following the Outbreak of Sars-Cov-2 Omicron Variant in Shanghai

Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessening the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Method(s): To investigate whether inactivated vaccines were effective in protecting against COVID-19 infections, we estimated the odds ratio (OR) of the vaccination in COVID-19 cases vs. matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied the multivariate stepwise Logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Result(s): Out of the 153,544 COVID-19 patients included in the analysis, 118,124 (76.9%) patients had been vaccinated and 143,225(93.3%) were asymptomatic patients. Of the 10,319 symptomatic patients, 10,031(97.2%), 281(2.7%) and 7(0.1%) experienced mild, moderate, and severe infections, respectively. There is no evidence that the vaccination helped protect from infections (OR=0.82, p=0.613). The vaccination, however, offered a small but significant protection against symptomatic infections (RR=0.92, p < 0.001) and halved the risk of moderate/severe infections (OR=0.48, 95% CI: 0.37 - 0.61). Older age (> 60 years) and malignant tumors were significantly associated with moderate/severe infections. Gender also appeared to be a risk factor for symptomatic infections, with females being associated with a lower risk for moderate/severe illness. Conclusion(s): Inactivated COVID-19 vaccines helped provide a small but significant protection against symptomatic infections and halved risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking COVID-19 Omicron variant community spread.Copyright © 2023

Clinical Characteristics of Patients with Sars-Cov-2 Omicron Variant and COVID-19 Vaccination with Clinical Outcome Findings in Shanghai, China: A Single Center, Retrospective, Observational Study

Objectives: This study aimed to determine disease severity, clinical features, clinical outcome in hospitalized patients with the Omicron variant and evaluate the effectiveness of one-dose, two-dose, and three-dose inactivated vaccines in reducing viral loads, disease course, ICU admissions and severe diseases. Method(s): Retrospective cohort analysis was performed on 5,170 adult patients (>=18 years) identified as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction admitted at Shanghai Medical Center for Gerontology between March 2022 and June 2022. COVID-19 vaccination effectiveness was assessed using logistic regression models evaluating the association between the risk of vaccination and clinical outcomes, adjusting for confounders. Result(s): Among 5,170 enrolled patients, the median age was 53 years, and 2,861 (55.3%) were male. 71.0% were mild COVID-19 cases, and cough (1,137 [22.0%]), fever (592 [11.5%]), sore throat (510 [9.9%]), and fatigue (334 [6.5%]) were the most common symptoms on the patient's first admission. Ct values increased generally over time and 27.1% patients experienced a high viral load (Ct value< 20) during their stay. 105(2.0%) of these patients were transferred to the intensive care unit after admission. 97.1% patients were cured or showed an improvement in symptoms and 0.9% died in hospital. The median length of hospital stay was 8.7+/-4.5 days. In multivariate logistic analysis, booster vaccination can significantly reduce ICU admissions and decrease the severity of COVID-19 outcome when compared with less doses of vaccine (OR=0.75, 95%CI, 0.62-0.91, P<=0.005;OR=0.99, 95%CI, 0.99-1.00, p<0.001). Conclusion(s): In summary, the most of patients who contracted SARSCoV-2 omicron variant had mild clinical features and patients with vaccination took less time to lower viral loads. As the COVID-19 pandemic progressed, an older and less vaccinated population was associated with higher risk for ICU admission and severe disease.Copyright © 2023

Comparison of Immediate Adverse Effects of COVID-19 Vaccine (COVAXIN BBV152) in Pregnant vs Nonpregnant Women

Aims and objectives: The aim of this study was to compare the immediate adverse effects of the coronavirus disease 2019 (COVID-19) vaccine (COVAXIN) in a pregnant woman with that of a nonpregnant woman. Material(s) and Method(s): It is a prospective observational study done at Vanivilas Hospital, Bangalore Medical College & Research Institute (BMCRI) for 2 months. The sample size was 100 pregnant and 100 nonpregnant women. Telephonically, patients were followed-up, and details of the side/adverse effects were collected in a proforma after 2 and 14 days. Data collected from both groups were analyzed using the Chi-square test or Fisher's exact test. Result(s): The majority of women were in the age group of <=25 years (64.0% and 36.0%, respectively) with a mean age of 25.01 +/- 3.71 years among the pregnant and 28.52 +/- 6.00 years among nonpregnant women. About 25.0% of pregnant women and 38.0% of nonpregnant women reported side effects. About 15.0% and 22.0% had taken treatment for side effects among pregnant women and nonpregnant women, respectively. Among the pregnant women, the common side effects reported were injection site pain (17) followed by fever (5), fatigue (4), and myalgia (03). Whereas among the nonpregnant women, the common side effects reported were injection site pain (28) followed by fever (6), myalgia (3), headache (2), and fatigue (1). Conclusion(s): Side effects reported following the administration of Covaxin in pregnant and nonpregnant women are fever, fatigue, injection site pain, myalgia, and headache. The proportion of side effects was not significantly different in the pregnant and nonpregnant women following Covaxin administration. Clinical significance: Covaxin is an inactivated killed vaccine against COVID-19 by Bharat Biotech. The vaccine has been recommended for pregnant women by the Government of India during corona pandemic. Studies are lacking regarding the difference in adverse events in pregnant versus nonpregnant women, after vaccine administration.Copyright © The Author(s).

Animal Pre-Clinical Study of an Inactivated SARS-CoV-2 Vaccine candidate (Osvid-19 ): Immunogenicity, Protective, and Safety Aspects

Background: This study aimed to evaluate the outcomes of preclinical studies on the safety and immunogenicity of an inactivated COVID-19 vaccine candidate to warrant further clinical evaluation. Method(s): SARS-CoV-2 positive nasopharyngeal swab specimens were confirmed by real-time polymerase chain reaction and next-generation sequencing. The safety and immunogenicity tests of the COVID-19 vaccine were carried out in rats and Rhesus monkeys, and Balb/C mice and Rhesus monkeys, respectively. Result(s): The candidate vaccine was well tolerated and induced promising levels of SARS-CoV-2- specific IgG1, IgG2a, and Granzyme B in Balb/C mice, and anti-SARS-CoV-2 spike IgG and neutralizing antibodies in Rhesus monkeys. Based on cVNT results, the inactivated vaccine in 0.5 and 1 microg/100 microL doses was able to induce a neutralizing effect against the SARS-CoV-2 virus up to a dilution of 1:512 and 1:1000. The protective efficacy of the vaccine candidate was challenged with 2 x108 PFU of live viruses and confirmed by lung CT scan and histopathological evaluations compared to the control group. Repeated intramuscular injection of the candidate vaccine was generally well-tolerated in Rats and Rhesuses. No significant side effects were observed in rats injected with ten full human doses and in the Rhesus monkeys with three full human doses. Conclusion(s): Based on the findings presented in this study, it is recommended that this vaccine be moved into human testing commencing with a phase I clinical trial.Copyright © 2021 Muslim OT et al.

Monitoring SARS CoV-2 antibodies positivity in healthcare workers after inactivated CoronaVac vaccine

Introduction In this study, we aimed to monitor anti-spike and anti-nucleocapsid antibodies positivity in healthcare workers (HCWs) vaccinated with two doses of inactivated CoronaVac (Sinovac, China) vaccine. Methods Overall, 242 volunteer HCWs were included. Of the participants, 193 were HCWs without history of prior documented COVID-19 (Group 1), while 49 had history of prior documented COVID-19 before vaccination (Group 2). The participants were followed up for SARS-CoV-2 antibodies positivity at four different blood sampling time points (immediately before the second vaccine dose and at the 1st, 3rd months and 141-150 days after the second dose). We investigated the serum IgG class antibodies against SARS-CoV-2 RBD region and IgG class antibodies against SARS-CoV-2 nucleocapsid antigen by chemiluminescent microparticle immunoassay (CMIA) method using commercial kits. Results We found positive serum anti-RBD IgG antibody in 76.4% of the participants (71% in Group 1;98% in Group 2) 28 days after the first dose. When the antibody levels of the groups were compared at the four blood sampling time points, Group 2 anti-RBD IgG levels were found to be significantly higher than those in Group 1 at all follow-up time points. Although anti-RBD IgG positivity persisted in 95.6% of all participants in the last blood sampling time point, a significant decrease was observed in antibody levels compared to the previous blood sampling time point. Anti-nucleocapsid IgG antibody was positive in 12 (6.2%) of participants in Group 1 and 32 (65.3%) in Group 2 at day 28 after the first dose. At the fourth blood sampling time point, anti-nucleocapsid antibodies were found to be positive in a total of 20 (9.7%) subjects, 10 (6.1%) in Group 1 and 10 (23.8%) in Group 2. Conclusions In this study, it was determined that serum antibody levels decreased in both groups after the third month after the second dose in HCWs vaccinated with CoronaVac vaccine.Copyright © GERMS 2022.

The Impact of Vaccination Time on the Antibody Response to an Inactivated Vaccine against SARS-CoV-2 (IMPROVE-2): A Randomized Controlled Trial.

There is still controversy about whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at different times of day will induce a stronger immune response. Therefore, a randomized controlled trial (ChiCTR2100045109) is conducted to investigate the impact of vaccination time on the antibody response to the inactivated vaccine against SARS-CoV-2 from April 15 to 28, 2021. Participants are randomly assigned in a 1:1 ratio to receive inactivated SARS-CoV-2 vaccine in the morning or afternoon. The primary endpoint is the change of neutralizing antibody between baseline and 28 days after the second dose. In total, 503 participants are randomized, and 469 participants (238 in the morning group and 231 in the afternoon group) complete the follow-up. There is no significant difference in the change of neutralizing antibody between baseline and 28 days after the second dose between the morning and afternoon groups (22.2 [13.2, 45.0] AU mL-1  vs 22.0 [14.4, 40.7] AU mL-1 , P = 0.873). In prespecified age and sex subgroup analyses, there is also no significant difference in the morning and afternoon group (all P > 0.05). This study demonstrates that the vaccination time does not affect the antibody response of two doses of inactivated SARS-CoV-2 vaccine.

Safety profile of inactivated COVID-19 vaccine in indonesian adults.

Background: Vaccines are urgently needed to handle the morbidity and mortality of the COVID-19 pandemic in Indonesia. The inactivated vaccine is widely used in Indonesia's national immunization program due to its eligibility of stock, easier to transport, and considered to be more established than newer platforms. In this study, we aimed to evaluate the safety profile of the inactivated vaccine and analyze the safety profile between adults and the elderly. Methods: A prospective analytical study was conducted to evaluate the safety profile of inactivated COVID-19 vaccine among healthy adults aged ≥ 18 years from September 2nd to December 28th, 2021, at ten primary health centers from 5 districts in Jakarta, Indonesia. The participants were instructed to record the symptoms after inactivated COVID-19 vaccine injection in the diary card for 28 days. Chi-square tests were carried out to analyze the relationship between the adverse event following immunization (AEFI) in adults and elderly groups. Results: Four of 1113 participants were not included in this study due to the lack of follow-up. Out of 1109 participants, there were 1044 adults (18-59 years) and 65 elderly (>59 years). There were no serious AEFI cases reported. Most AEFI cases were mild to moderate and resolved after several days of injection. Local pain, myalgia and fatigue were the most frequent adverse events reported. We found that there was no correlation between the adults and elderly age group with the incidence of AEFI (p = 0.924) for local reactions (p = 0.181) and most of the systemic reactions (p = 0.629). However, there is an increased risk of fever in the elderly group compared to the adult group (OR 4.046, 95 % CI 1.794-9.124, p = 0.003) following immunization. Conclusions: Our study demonstrated that the inactivated COVID-19 vaccine is safe, considering that all symptoms experienced were mild to moderate and resolved entirely.

Heterologous vaccination with inactivated vaccine and mRNA vaccine augments antibodies against both spike and nucleocapsid proteins of SARS-CoV-2: a local study in Macao.

The mRNA vaccines (RVs) can reduce the severity and mortality of severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, almost only the inactivated vaccines (IVs) but no RVs had been used in mainland China until most recently, and the relaxing of its anti-pandemic strategies in December 2022 increased concerns about new outbreaks. In comparison, many of the citizens in Macao Special Administrative Region of China received three doses of IV (3IV) or RV (3RV), or 2 doses of IV plus one booster of RV (2IV+1RV). By the end of 2022, we recruited 147 participants with various vaccinations in Macao and detected antibodies (Abs) against the spike (S) protein and nucleocapsid (N) protein of the virus as well as neutralizing antibodies (NAb) in their serum. We observed that the level of anti-S Ab or NAb was similarly high with both 3RV and 2IV+1RV but lower with 3IV. In contrast, the level of anti-N Ab was the highest with 3IV like that in convalescents, intermediate with 2IV+1RV, and the lowest with 3RV. Whereas no significant differences in the basal levels of cytokines related to T-cell activation were observed among the various vaccination groups before and after the boosters. No vaccinees reported severe adverse events. Since Macao took one of the most stringent non-pharmaceutical interventions in the world, this study possesses much higher confidence in the vaccination results than many other studies from highly infected regions. Our findings suggest that the heterologous vaccination 2IV+1RV outperforms the homologous vaccinations 3IV and 3RV as it induces not only anti-S Ab (to the level as with 3RV) but also anti-N antibodies (via the IV). It combines the advantages of both RV (to block the viral entry) and IV (to also intervene the subsequent pathological processes such as intracellular viral replication and interference with the signal transduction and hence the biological functions of host cells).

Safety and Efficacy of Covid-19 Immunization in Systemic Vasculitides - a Multicentric Cohort

Objectives: Patients with immune-mediated rheumatic diseases (IMRDs) develop more severe outcomes of Coronavirus disease 2019 (COVID-19). Recent studies have contributed to understand the safety and efficacy of COVID-19 vaccines in IMRDs, suggesting that different diseases and therapies may interfere on immunization efficacy. In this study we analyze the immunogenicity of COVID-19 vaccines in patients with Systemic Vasculitides (VASC), the rate of COVID-19 and the frequency of disease relapse following immunization. Method(s): We included patients with VASC (n = 73), a subgroup of the SAFER study (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease), a longitudinal, multicenter, Brazilian cohort.We analyzed the geometric means of IgG antibody against receptor-biding domain of protein spike of SARS-CoV-2 (anti-RBD) after two shots of CoronaVac (Inactivated vaccine), ChadOx-1 (AstraZeneca) or BNT162b2 (Pfizer-BioNTech). IgG anti-RBD was measured by chemiluminescence test. We assessed new-onset COVID-19 episodes, adverse events (AE) and disease activity for each VASC. Result(s): The sample included Behcet's disease (BD) (n = 41), Takayasu arteritis (TAK) (n = 15), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (n = 14), polyarteritis nodosa (n = 7) and other small vessel VASC(n = 6). The majority of patients were female (69%) without comorbidities (49%) and a median age of 37 years. The most common medication was conventional synthetic disease-modifying anti-rheumatic drugs, followed by biologic drugs. No patient received rituximab at baseline. Most patients received CoronaVac (n = 25) or ChadOx-1 (n = 36), while four received BNT162b2. Baseline IgG-RBD means were 1.34 BAU/mL. They increased to 3.89 and 5.29 BAU/mL after the 1st and 2nd vaccine dose, respectively. ChadOx-1 had higher antibody titers than CoronaVac (p = 0.002). There were no differences between different VASC. There were 3 cases of COVID-19 after immunization with CoronaVac. BD patients had a tendency for more cutaneous-articular activity following ChadOx-1. There were no severe relapses and no serious adverse events. Conclusion(s): Our results show the safety of different SARS-CoV-2 vaccines in VASC population. A progressive increase of IgG-RBD antibodies was observed after each dose. ChadOx-1 led to higher IgG-RBDgeometricmeans compared toCoronaVac. Finally, even though ChadOx-1 presented a tendency of triggering mild disease activity, there were no significant disease activity following vaccination in VASC patients. .

Safety surveillance of covid-19 vaccines using large-linked database

In the global drive to vaccinate against SARS-CoV-2, millions of people have received at least one dose of a COVID- 19 vaccine. Vaccination safety is the key to the success of immunisation programs and in combating vaccine hesitancy among the public. Post-licensure safety monitoring of COVID-19 vaccines is essential to detect rare or severe vaccine-associated adverse events in the population and provide ongoing data of safety issues. Passive surveillance is the primary method most widely used to collect adverse events following immunisation (AEFI) via voluntary reporting. Monitoring through active surveillance is strongly encouraged to improve vaccine safety monitoring and provide more robust data. The SAFECOVAC project was initiated to evaluate risk of serious adverse events following COVID-19 vaccination. It leverages on the availability of nationwide COVID- 19 vaccine registry, hospital admission database, and other data sources to create a large-linked database. Uniquely for Malaysia, diverse vaccine portfolio was used and we are able to compare the risk estimate for the three major vaccine types of different platform i.e., mRNA-based vaccine (BNT162b2), inactivated vaccine (CoronaVac), and adenovirus vector-based vaccine (ChAdOx1). Current data shows that safety of COVID-19 vaccine is assured and findings are fairly consistent with data from other countries.

Antibody response to SARS-CoV-2 WT and Omicron BA.4/5 of inactivated COVID-19 vaccine in patients with lung cancer after second and booster immunization.

COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4+T cells and CD8+T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.

Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21-105 days after full-course inactivated COVID-19 vaccination. The overall incidence of adverse events (AEs) was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

The Actual Status of Hospitals as COVID-19 Vaccination Clinics in China and Safety Monitoring of Inactivated Vaccine: A Cross-Sectional Study.

BACKGROUND: The outbreak has had a devastating impact, and efforts are underway to speed up vaccination. The study's objective was to describe the clinical characteristics of the coronavirus disease 2019 (COVID-19) vaccination clinic in the Second People's Hospital of Fujian Province, China. Meanwhile, we monitored all the vaccine recipients to evaluate adverse reactions. METHODS: A cross-sectional study was done at the COVID-19 Vaccination Clinic, the Second People's Hospital of Fujian Province, China. We systematically collected Clinical data from the COVID-19 vaccination clinic between March 11 and November 11, 2021, including the type of vaccine, number of doses, gender, age, educational level, occupational category, adverse reactions, etc. Investigators will contact vaccine recipients by means of phone call or WeChat message to record the negative responses. Last, this report covers data through 8 mo, so it will be better to Evaluate the Safety of 2 inactivated COVID-19 vaccines from China (BBIBP-CorV [Beijing Institute of Biological Products, Beijing, China] and CoronaVac [Sinovac Life Sciences, Beijing, China]). RESULTS: The results indicated that the Second People's Hospital of Fujian Province received a total of 64,602 COVID-19 vaccines from March 11 to November 11, 2021, including 34,331 (53.14%) first doses, 29,245 (45.27%) second doses, and 1026 (1.59%) third doses. This study found the highest proportion in other personnel (38.69% at the first dose, 38.75% at the second dose, and 2.44% at the third dose), who were mainly retirees. People with higher levels of education are more likely to be vaccinated against COVID-19 during the early stages of vaccine rollout. In terms of age stratification, the highest proportion was found among people aged 18-49 (BBIBP-CorV: first dose 61%, second dose 62.6%, and third dose 76.8%; CoronaVac: first dose 66.1%, double dose 63.6%, and third dose 75.5%), followed by those over 60. The common adverse reactions were mainly local and systemic, and there were some differences between the 2 inactivated vaccines (P < 0.05). CONCLUSIONS: This is the first study to analyze the actual status of hospitals as COVID-19 vaccination clinics in China. The hospital has focused on vaccinating citizens and the initial rollout of vaccines to ensure any safety issues are identified. More citizens are willing to vaccinate in hospitals because of the uncertain safety of the available vaccines and adverse reactions. The good news is that vaccine-related severe adverse events have not been found in the hospital vaccination clinic. The Safety of BBIBP-CorV and CoronaVac is relatively high.

Coronavirus disease 2019 vaccination in patients with chronic kidney diseases.

Patients with chronic kidney disease (CKD) are at high risk for coronavirus disease 2019 (COVID-19). Government agencies or learned societies in many countries recommend prioritizing patients with CKD for COVID-19 vaccines. The immune response rate to the COVID-19 vaccines is lower in hemodialysis patients and kidney transplant recipients compared with that in healthy individuals, and increasing the number of vaccinations each member of these population may improve their immune response rate. There was no significant difference in the incidence of adverse reactions after vaccination between patients with CKD and healthy controls. Patients with stable CKD should be vaccinated against COVID-19 unless there were contraindications to vaccination. The mRNA vaccines, inactivated vaccines, and recombinant protein subunit vaccines are all safe for patients with CKD. Patients with CKD treated with rituximab or high-dose glucocorticoid need to weigh the benefits and risks before vaccination, and COVID-19 vaccines can be given when rituximab treatment ends for more than 6 months or after glucocorticoid reduction.Copyright © 2021 by the Chinese Medical Association.

Vaccines for the prevention of infections in adults with haematological malignancies

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and adverse effects of vaccines for the prevention of infections in adults with haematological malignancies.Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Evaluation of the immunogenicity of an inactivated vaccine prototype against SARS-COV- 2 virus in vitro

Background: Belarus started developing a vaccine against SARS-CoV- 2 in 2021. The aim of the first stage of investigation was to evaluate the immunogenicity of the vaccine prototypes (VP) in vitro. Method(s): SARS-CoV- 2 strains (n = 7) were isolated using Vero E6 cells, inactivated with beta-propiolactone and purified. Antigens (Ag) were adsorbed on adjuvants: Al(OH)3 (Ag+AH group) or Al3PO4 (Ag+AP group). The single dose of VP (500 ul) was composed of 10 mug of Ag adsorbed on adjuvants (200 mug of Al3+). Blood samples from SARS-CoV- 2 recovered donors (n = 18) and healthy controls having no history of COVID-19 infection (n = 5) were used. Whole blood and Tag-it Violet labeled PBMCs were cultivated with VP, pure Ag, adjuvants (0.25-1 mug of Ag, 20 mug of Al3+ for probe) or pool of peptides, covering sequence of SARS-CoV- 2 N, S, M-proteins (PP), for 6 h and 7 days respectively. INF-gamma production and proliferation of CD3+ T-cells were assayed by FACS. Result(s): Counts of CD3+IFN-gamma+ T cells were 3.14(2.72-5.13)/ 1x105 CD3+ T cells in negative control (NC), and 12.73(10.09-33.95)/ 1x105 CD3+ T cells in specific positive control (PP) (n = 18, p < 0.0001), proving presence of antigen-specific T cells (ASCs) in donor blood. Samples were considered positive for VP and Ag immunogenicity when numbers of CD3+IFN-gamma+ T cells were 1.5 times greater compared with NC. Both VP types (Ag+AP, Ag+AH) and pure SARS-CoV- 2 isolates stimulated the production of INF-gamma by ASCs, responses ranged from 1 to 4 isolates of 7 studied per donor. Immunogenicity of Ag+AP, Ag+AH was confirmed by proliferation assay. Proliferation level was 1.07(0.97-2.38)% in Ag group with no differences from NC (n = 7, p > 0.5). Proliferation was significantly greater in VP groups compared with Ag: 2.47(1.65-2.68)% in Ag+AH, 4.03(2.56-4.61)% in Ag+AP (p = 0.009 and 0.002, respectively), stimulation of T cell was stronger by Ag+AP compared with Ag+AH (p = 0.009, M-U test). Pure adjuvants did not induce T cells response. There was no T-cell stimulation by Ag and VP in samples obtained from COVID-19 negative donors. Conclusion(s): The VP against SARS-CoV- 2 infection composed of inactivated virus adsorbed on Al(OH)3 and Al3PO4 adjuvants has immunogenic properties proven in two different immunological assays. VP stimulated activation and proliferation of ASCs in vitro suggesting this VP can be used for further preclinical in vivo evaluation.

Immunodominant SARS-CoV-2-specific CD4+ and CD8+ T-cell responses elicited by inactivated vaccines in healthy adults.

Safety profiles and humoral responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been previously assessed, but cellular immune responses to inactivated SARS-CoV-2 vaccines remain understudied. Here, we report the comprehensive characteristics of SARS-CoV-2-specific CD4+ and CD8+ T-cell responses elicited by the BBIBP-CorV vaccine. A total of 295 healthy adults were recruited, and SARS-CoV-2-specific T-cell responses were detected after stimulation with overlapping peptide pools spanning the entire length of the envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins. Robust and durable CD4+ (p < 0.0001) and CD8+ (p < 0.0001) T-cell responses specific to SARS-CoV-2 were detected following the third vaccination, with an increase in specific CD8+ T-cells, compared to CD4+ T-cells. Cytokine profiles showed that interferon gamma and tumor necrosis factor-α were predominantly expressed with the negligible expression of interleukin (IL)-4 and IL-10, indicating a Th1- or Tc1-biased response. Compared to E and M proteins, N and S activated a higher proportion of specific T-cells with broader functions. The predominant frequency of the N antigen (49/89) was highest for CD4+ T-cell immunity. Furthermore, N19-36 and N391-408 were identified to contain dominant CD8+ and CD4+ T-cell epitopes, respectively. In addition, N19-36 -specific CD8+ T-cells were mainly effector memory CD45RA cells, whereas N391-408 -specific CD4+ T-cells were mainly effector memory cells. Therefore, this study reports comprehensive features of T-cell immunity induced by the inactivated SARS-CoV-2 vaccine BBIBP-CorV and proposes highly conserved candidate peptides which may be beneficial in vaccine optimization.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study.

BACKGROUND: Vaccines that prevent SARS-CoV-2 infection are considered the most promising approach to modulating the pandemic. There is scarce evidence on the efficacy and safety of different vaccine prime-boost combinations in MHD patients since most clinical trials have used homologous mRNA vaccine regimens. METHODS: This prospective observational study assessed the immunogenicity and safety of homologous CoronaVac® (SV-SV), ChAdOx1 nCoV-19 (AZD1222) (AZ-AZ), and the heterologous prime-boost of SV-AZ, among MHD patients. RESULTS: A total of 130 MHD participants were recruited. On day 28, after the second dose, seroconversion results of the surrogate virus neutralization test were not different between vaccine regimens. The magnitude of the receptor-binding domain-specific IgG was highest among the SV-AZ. Different vaccine regimens had a distinct impact on seroconversion, for which the heterologous vaccine regimen demonstrated a higher probability of seroconversion (OR 10.12; p = 0.020, and OR 1.81; p = 0.437 for SV-AZ vs. SV-SV, and SV-AZ vs. AZ-AZ, respectively). There were no serious adverse events reported in any of the vaccine groups. CONCLUSIONS: Immunization with SV-SV, AZ-AZ, and SV-AZ could generate humoral immunity without any serious adverse events among MHD patients. Using the heterologous vaccine prime-boost seemed to be more efficacious in terms of inducing immunogenicity.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.